scholarly journals Effect of Huai Qi Huang on Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells through miR-200a

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Jinyun Pu ◽  
Yu Zhang ◽  
Jianhua Zhou

Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells is a vital mechanism of renal fibrosis. Mounting evidence suggests that miR-200a expression decreases in tubular epithelial cells in unilateral ureteral obstruction (UUO) rats. Moreover, it has been demonstrated that Huai Qi Huang (HQH) can ameliorate tubulointerstitial damage in adriamycin nephrosis and delay kidney dysfunction in primary glomerular disease. However, the effect of HQH on EMT of tubular epithelial cells in UUO rats and its molecular mechanism is unclear. In order to explore the effect of HQH on EMT and its molecular mechanism in renal fibrosis,in vitroandin vivoexperiments were performed in our study. Our results showed that HQH increased miR-200a expression in UUO rats and in TGF-β1 stimulated NRK-52E cells. Meanwhile, HQH decreased ZEB1 and ZEB2 (the transcriptional repressors of E-cadherin),α-SMA expression in renal tubular epithelial cellsin vitroandin vivo. Furthermore, we found that HQH protected kidney from fibrosis in UUO rats. The results demonstrated that HQH regulated miR-200a/ZEBs pathway and inhibited EMT process, which may be a mechanism of protecting effect on tubular cells in renal fibrosis.

2017 ◽  
Vol 46 (4) ◽  
pp. 333-342 ◽  
Author(s):  
Huifang Liu ◽  
Jiachuan Xiong ◽  
Ting He ◽  
Tangli Xiao ◽  
Yan Li ◽  
...  

Background: Hyperuricemia is an independent risk factor for causing chronic kidney disease and contributes to kidney fibrosis. After urate crystals get deposited in the kidney, they can cause hyperuricemia nephropathy, leading to glomerular hypertrophy and renal tubular interstitial fibrosis. Recent data showed that uric acid (UA) could induce epithelial mesenchymal transition (EMT) of renal tubular cells, in which NRLP3 inflammatory pathway was involved. However, whether TLR4/NF-κB signaling pathway is also involved in EMT of renal tubular cells induced by UA is not clear. Methods: Human renal tubular epithelial cells (HK-2) were directly treated with UA and the phenotypic transition was detected by morphological changes and the molecular markers of EMT. The activation of the TLR4/NF-κB signaling pathway induced by UA was measured by Western blot and its involvement was further confirmed by the inhibition of NF-κB activation or knockdown of toll like receptor 4 (TLR4) expression. Results: UA induced obvious morphological changes of HK-2 cell, accompanied with altered molecular markers of EMT including fibronectin, α-SMA and E-cadherin. In addition, UA significantly upregulated the gene expression of interleukin-1β and tumor necrosis factor-α in a time- and dose-dependent manner. Furthermore, UA significantly activated the TLR4/NF-κB signaling pathway in HK-2 cells, while the inhibition of the TLR4 expression by siRNA and NF-κB activation by PDTC significantly attenuated EMT induced by UA in HK-2 cells. Conclusions: UA can induce EMT in renal tubular epithelial cells by the activation of the TLR4/NF-κB signaling pathway, and the targeted intervention of the TLR4/NF-κB signaling pathway might effectively inhibit UA-induced renal interstitial fibrosis mediated by EMT.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Li-Cai Zhang ◽  
Zong-Bin Wei ◽  
Shui-Fu Tang

Renal fibrosis, the leading cause of end-stage renal disease and in which epithelial-mesenchymal transition (EMT) plays a central role, has a complex pathogenesis that is not fully understood. Therefore, we investigated the role of the long noncoding RNA LUCAT1 in the EMT of renal tubular epithelial cells under high-glucose (HG) conditions and the underlying mechanism involved. In this study, we established HG and normal glucose groups of HK-2 cells by treating HK-2 cells 30.0 or 5.5 mmol/L glucose, respectively. To investigate the roles of LUCAT1 and miR-199a-5p in HG-induced EMT, we transfected the HG group with negative control small interfering RNA (siRNA), siRNA targeting LUCAT1, negative control microRNA, or an miR-199a-5p mimic. The results of the quantitative reverse transcription PCR indicated that the LUCAT1 level in the HG group was increased, whereas the miR-199a-5p level was decreased. The EMT in the cells was induced by treatment with HG but was weakened by LUCAT1 knockdown or miR-199a-5p overexpression, which both also inhibited the HG-induced phosphorylation of SMAD3. Moreover, LUCAT1 and ZEB1 mRNA comprised the same microRNA response elements of miR-199a-5p. LUCAT1 knockdown had no effect on the miR-199a-5p level but decreased the HG-induced upregulation of ZEB1. In conclusion, HG conditions induced the upregulation of LUCAT1, and LUCAT1 knockdown inhibited the EMT in HG-treated HK-2 cells. LUCAT1 likely promotes HG-induced EMT through ZEB1 by sponging miR-199a-5p.


Sign in / Sign up

Export Citation Format

Share Document